In 2014, spurred on by research taking place in the US, NHS consultant psychiatrist Rupert McShane headed up the first UK study(Diamond et al., 2014) on the drug as a treatment for depression.

“The results of the study were the sort of thing that makes it all worthwhile—it reminded me a bit of the film Awakenings . . . We had one patient who was very sick, had ketamine, and got sufficiently well that they were able to write a really complicated, competitive grant application. They then won that grant,” says McShane.

A chemical byproduct, or metabolite, created as the body breaks down ketamine likely holds the secret to its rapid antidepressant action, National Institutes of Health (NIH) scientists and grantees have discovered.

The NIH study found that this metabolite singularly reversed depression-like behaviors in mice without triggering any of the anesthetic, dissociative, or addictive side effects associated with ketamine.

“This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works and holds promise for development of more robust and safer treatments,” said Carlos Zarate, M.D. of the NIH’s National Institute of Mental Health (NIMH), a study co-author and a pioneer of research using ketamine to treat depression.